The long range objective of the research outlined in this proposal is to characterize neural control mechanisms of resistance and capacitance blood vessels of the splanchnic circulation and determine mechanisms which underlie differential regulation of these two vascular networks. The proposed studies will compare sympathetic co-transmission in guinea pig mesenteric artery and vein. The PI hypothesizes that responses to nerve stimulation in vein and artery differ because: (1) the mechanisms which are initiated by ATP and norepinephrine (NE) in smooth muscle differ and/or (2) the amount and/or ratio of ATP and NE at the vicinity of the postjunctional receptor differ. Specific Aims 1 and 2 will address the first part of this hypothesis by characterizing the effects of exogenous and endogenous NE and ATP on membrane potential (intracellular microelectrode techniques) and force development (organ bath experiments) in artery and vein and determining whether different subtypes of P2 purinergic and alpha-adrenergic receptors are involved. Specific Aim 3 will address the second part of this hypothesis by employing state-of-the-art techniques to simultaneously measure nerve evoked outflow of ATP (HPLC-fluorscence detection) and NE (HPLC- electrochemical detection) in artery and vein. Thus, mesenteric artery and vein will be uniquely compared in terms of both transmitter release and postjuctional effector mechanisms. These studies will provide new insights into the differential control of arteries and veins by nerves. They will also aid in clarifying the role of ATP as a neurotransmitter in the splanchnic circulation and its relationship to NE as the primary sympathetic neurotransmitter.